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K K Ang

Publications and source records attributed to K K Ang.

At least 127 records · Page 7Linked to original sources
PubMed1989

The high steepness of dose-response curves for late-responding normal tissues.

Values are calculated for the parameters alpha, beta, and the number of tissue-rescuing units (TRU), which together describe the location and the steepness of dose-incidence curves for functional injury in various normal tissues. The analysis is based on a Poisson model of the distribution of surviving TRUs. The steepness of the curves for early-responding tissues has been shown previously to be compatible with values of sensitivity for the target colony-forming cells in these tissues. We now show that the steepness of curves for late responses in spinal cord, lung, and kidney is higher by a factor of up to 3 than the steepness of curves for early responses in other tissues. Although the interpretation of this higher steepness is not fully understood, this observation is likely to be of importance for radiotherapy.

Animals↗
PubMed1989

Hyperfractionated radiotherapy in the treatment of squamous cell carcinomas of the supraglottic larynx.

From January 1984 through December 1987, 41 patients with squamous cell carcinomas of the supraglottic larynx were treated with hyperfractionated radiotherapy at The University of Texas M. D. Anderson Cancer Center. Two patients had T1 primary tumors, 23 had T2, 15 had T3, and 1 had T4; 29 patients had no clinical evidence of nodal disease in the neck, 4 had N1, 5 had N2, and 3 had N3. Radiotherapy was delivered in 120 cGy fractions twice per day, with at least 4 hr between treatments. Total doses ranged from 7200 to 7900 cGy (median, 7680 cGy). Three patients had planned neck dissections before or after radiotherapy, and three patients with fixed vocal cord lesions were treated with preradiation chemotherapy. At the time of analysis, median follow-up was 22 months. Four patients have had failures at the primary tumor site. There has been one recurrence in the neck in a patient who also had a recurrence at the primary site. Three of the four patients with recurrences have been successfully treated with salvage surgery. Exclusive of surgical salvage, the actuarial disease-free local control rates above the clavicles in the 38 patients with T2 and T3 cancers were 96% at 1 year and 87% at 2 years. In comparison, the rates were 82% and 76% for a group of 98 patients with T2 and T3 lesions treated at this institution from 1970 to 1981 with 6500-7000 cGy given in 200 cGy fraction per day. As predicted, acute reactions were more severe but late complications were not increased in patients who received hyperfractionated radiotherapy compared with those treated by conventionally fractionated therapy. Only two patients have developed severe late complications one of whom required laryngectomy. Hyperfractionated radiotherapy appears to provide improved local control with a similar incidence of late complications when compared with conventionally fractionated therapy. To further improve the therapeutic ratio, our current protocol has been amended by reducing the large field dose per fraction to 110 cGy (with a 2 day protraction of overall time) and requiring a minimum interfraction interval of 6 hr.

Adult↗
PubMed1989

Effects of high dose intraperitoneal cytosine arabinoside on the radiation tolerance of the rat spinal cord.

The effect of intraperitoneal high dose (9 g/kg) Cytosine Arabinoside (Ara-C) on the early delayed radiation response of the rat cervical spinal cord has been studied. When given 2 hrs before irradiation, systemically administered Ara-C significantly reduces the isoeffect doses for the induction of paralysis due to white matter necrosis by a factor of approximately 1.2 for both a single irradiation treatment and for a two fraction irradiation with 24 hr interval. No effect on the latency time to develop paralysis was recorded.

Animals↗
PubMed1989

Definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa.

Between July 1968 and December 1983, 150 patients with previously untreated squamous cell carcinomas of the tonsillar fossa received megavoltage external beam irradiation with curative intent at U.T.M.D. Anderson Cancer Center. These patients were treated following a series of patients who had received radiotherapy between 1954 and May 1968. One hundred and thirty-seven patients were treated with conventional fractionation, the mean doses to the primary being 64.3 Gy, 67.8 Gy, 70.2 Gy, and 72.6 Gy for T1, T2, T3, and T4 lesions respectively. Thirteen patients were treated by altered fractionation schedules, 7 by hyperfractionation, and 6 by a concomitant boost to the primary. Elective bilateral neck irradiation was routine in all patients. A planned neck dissection was performed in 26 patients. The 5-year actuarial overall and disease-specific survival rates were 47% and 70%, respectively. Absolute local control rates with a minimum of 2 years follow-up after irradiation were 94%, 79%, 58%, and 50% for patients with T1, T2, T3, and T4 disease respectively. A total of 37 patients had local treatment failure; in 5 of 18 surgical salvage was successful. Only 4 patients with primary disease control developed failure in the neck and none of those with N0 or N1 disease did so when the primary was controlled. Twelve patients developed transient self-limited bone exposure, 7 developed osteoradionecrosis of the mandible, all requiring surgical resection. Most severe late complications occurred in patients with T3 and T4 lesions whose dose to the primary exceeded 67.5 Gy.

Adult↗
PubMed1989

Direct estimation of latent time for radiation injury in late-responding normal tissues: gut, lung, and spinal cord.

Mixture models are proposed for simultaneous analysis of the latency and fractionation characteristics of radiation injury in late-responding normal tissues. The method is an extension of the direct analysis for quantal response data. Conceptually, the application of the mixture model is based on the biological observation that over a wide range of doses a proportion of the irradiated subjects will never express damage. Mixture models allow the time of occurrence to be utilized in the analysis. Furthermore, this type of model takes time-censored observations into account in a natural way and provides an adequate framework for modelling and analysis of effect-dependent latency. Mixture models with complete and incomplete repair are applied to dose-incidence data for four late endpoints in rodents: death from radiation-induced pneumonitis, leg paralysis after spinal-cord irradiation, and radiation-induced rectal stenosis and anal discharge. Radiation-induced pneumonitis had an effect-dependent latency. The modelling of this phenomenon correlates well with the results of histologic studies. Interestingly, the ratio of hazard rates was not constant for this endpoint. The dominating feature in the latency of radiation injury to the spinal cord was a strong dependency on dose per fraction. After correction for this effect a tendency towards a longer latent time for lower effect levels was observed. For the rectal complications, there was no difference between latency with radiation only vs. radiation combined with cis-platin.

Animals↗
PubMed1989

The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness.

The synergistic effect of total lymphoid irradiation with KCl-extracted donor type antigen (H-Ag) was examined in the rat cardiac graft model. TLI therapy alone of 10, 16, and 20 Gy achieved by a 2 Gy daily treatment of WFu recipients produced modest prolongation of BUF heart survival to median survival times (MST) of 11, 26, and 30 days, respectively, in comparison with normal control (MST = 6). The TLI immunosuppressive effect was significantly potentiated with donor H-Ag when combined with 16 (greater than 100 days) but not with 10 or 20 Gy TLI therapy. This effect was specific: 16 Gy TLI treated recipients of BUF hearts rejected their grafts in a MST of 27 days when treated with third-party BN H-Ag. The state of unresponsiveness was transferable to 6 Gy total-body-irradiated WFu recipients of BUF hearts with 60 x 10(6) purified T cells isolated from TLI/H-Ag-treated rats (greater than 100) but not from normal controls (MST = 6). In vitro analysis of nontransplanted WFu rats 1-4 weeks after completion of 16 Gy TLI therapy alone demonstrated a nonspecifically reduced MLR proliferative response as well as the presence of potent nonspecific suppressor cells (NSC). By 3 or even 6 months post-TLI, W3/25- NSC displayed persistent suppressive activity and inhibited normal proliferative response to alloantigens. Limiting dilution assay revealed that the frequency of T cytotoxic cells (fTc) was severely decreased to 1:63111 at one day and to 1:16488 at one week postirradiation in comparison with normal control (1:2551). At 3 and 6 months the fTc of 1:2301 and 1:2040, respectively, approximated normal levels. These combined in vivo and in vitro results demonstrate that 16 Gy TLI therapy induces an unresponsiveness mediated by NSC and that the administration of donor type H-Ag facilitates the generation of potent regulatory T cells capable of inducing prolonged heart allograft survival.

Animals↗
PubMed1989

Response of plateau-phase C3H 10T1/2 cells to radiation and concurrent administration of bleomycin.

The mode and extent of interaction between bleomycin and radiation were assessed in contact-inhibited cultures of C3H 10T1/2 cells, which in confluent monolayers display a low turnover rate and behave more like late-responding normal tissues in vivo with respect to response to fractionated radiotherapy (i.e., having a low alpha/beta value). Plateau-phase C3H 10T1/2 cultures were exposed to gamma rays delivered in 1, 2, 5, or 10 fractions. The radiation doses administered ranged from 2 Gy in one exposure to 26 Gy in 10 fractions. Half of the cultures were also treated with 1 micrograms/ml of bleomycin for 5 days during which radiation was also given. It was found that 1 micrograms/ml of bleomycin sterilized approximately 40% of the C3H 10T1/2 cells in the cultures. The radiation dose-survival curves of various fractionation schedules (1, 2, 5, and 10 fractions) plus bleomycin were displaced downward (i.e., to lower survival levels) but not modified in shape. The alpha/beta ratios, parameters of the linear-quadratic model of cell survival, were 2.6 (2.2-3.1) and 2.4 (1.8-3.1) Gy for radiation only and radiation plus bleomycin, respectively. This observation indicates that the effect of combining irradiation and bleomycin on C3H 10T1/2 cells in monolayers was additive.

Animals↗
PubMed1989

Glands of the eyelids of rhesus monkeys (Macaca mulatta).

The various glands of rhesus monkey eyelids and human eyelids are similar. Numerous modified sebaceous glands are located along the tarsus. These conform with the meibomian glands, while typical sebaceous glands associated with the hair follicles of the lashes are consistent with the glands of Zeis. Lobules of accessory lacrimal tissue, corresponding to the glands of Krause and Wolfring, are located in the conjunctiva of the fornix and along the orbital border of the tarsal plate. Goblet cells are plentiful in the mucosa of the palpebral and bulbar conjunctiva, and along the lid margin are the sweat glands of Moll.

Animals↗
PubMed1989

Response of parotid gland organ culture to radiation.

Organ cultures of rhesus parotid tissue in medium enriched with homologous serum and supplemented with low levels of isoproterenol were irradiated with single photon doses of 2.5, 5.0, 7.5, 10.0, 12.5, or 15.0 Gy. Following irradiation, the tissue was incubated while being agitated for 24 h; then it was fixed in formalin. Microscopically, death of serous acinar cells was seen in areas unaltered by autolysis. Based on the numbers of nuclear aberrations, the dose response did not differ significantly from that observed at 24 h in parotid gland irradiated in vivo. The similar rapid response under the two conditions shows that apoptosis of irradiated parotid serous cells is a direct expression of interphase cell death.

Animals↗
PubMed1988

Acute radiation injury of ocular adnexa.

Eyelids and lacrimal glands of monkeys examined histologically 24 and 48 hours after receiving 2.5 to 20.0 Gy (250 to 2000 rad) of cobalt 60 radiation contained acute inflammation. Cells of meibomian glands, other sebaceous glands, sweat glands, and goblet cells displayed no significant alterations. Acinar cells of major and accessory lacrimal glands and, to a lesser degree, lacrimal duct epithelium showed degeneration and necrosis that were increased in extent in proportion to the radiation dose. Reduced numbers of serous acini and decreased size of remaining acini indicate that atrophy of lacrimal glands can be recognized within two days after irradiation. The morphologic diagnosis for irradiated lacrimal glands was acute, necrotizing dacryoadenitis.

Acute Disease↗
PubMed1988

Unilateral kidney irradiation and late retreatment with cis-dichlorodiammineplatinum (II): functional measurements with 99mtechnetium-dimercaptosuccinic acid.

A rat model was used to study renal function after unilateral kidney irradiations. The left kidney was irradiated with a single dose (6-14 Gy), 2 equal sized fractions (10-16 Gy total dose) or 4 equal sized fractions (12 to 21 Gy total dose). At regular time intervals after treatment, the left kidney function was assessed with the use of 99mTc-Dimercaptosuccinic acid for a period of about 1 year. It was found that renal function declined in a dose- and time-dependent manner. The threshold dose for detecting functional impairment was 8 Gy for 1 fraction, 12 Gy for 2 fraction and 15 Gy for 4 fraction irradiations, demonstrating the sensitivity of the isotope tracer test used in these experiments. Retreatment of the rats with a single i.p. dose of 5 mg/kg cis-Dichlorodiammineplatinum (II) (cis-DDP) given at about 1 year after X ray exposure revealed an important relative decrease in the function of the irradiated compared to the unirradiated kidney. Reductions in function of 11 to 70% (depending on radiation dose and schedule) compared with control values were observed at 11 weeks after drug injection. These results demonstrate that a previously irradiated kidney is more sensitive to a subsequent treatment with cis-DDP than the contralateral hypertrophied kidney in the same animal.

Animals↗
PubMed1988

Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity.

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

Adult↗
PubMed1988

From 2 Gy to 1 Gy per fraction: sparing effect in rat spinal cord?

Recently published results, from this group, on rat cervical spinal cord, a late responding tissue, indicated no further sparing with lowering the fraction size from 2 to 1.8, 1.5, and 1.3 Gy. In the present experiments a small but probably significant rise in tolerance is suggested, when the dose per fraction was decreased from 2 Gy down to 1 Gy. This rise would however still be much less than what is predicted by the linear quadratic model, based on the experimental data obtained with fraction sizes larger than 2 Gy.

Animals↗
PubMed1988

Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction?

Recent evidence indicates that isoeffect doses for spinal cord and kidney may be overestimated for fraction sizes as small as 1 or 2 Gy when calculated from a linear-quadratic (LQ) model fitted to data obtained for fraction sizes larger than 2 Gy. Reasons for this are unknown, but possible interpretations include exhaustion of repair capacity and incomplete repair in experiments designed to study the response to these small doses. The latter interpretation is motivated by the relatively short intervals between multiple daily doses given to the spinal cord (4 h) and kidney (5 h) when fraction sizes were small. The possibility that overestimation of isoeffect dose could be explained by incomplete repair during short intervals between doses was assessed by fitting experimental data to the incomplete-repair model. For the spinal cord the data could be interpreted by assuming that a repair process with a half-time of 1.7 h was incomplete; this half-time is negligibly different from the estimate obtained from repair-kinetics experiments with larger doses per fraction. The deviation from the (complete-repair) LQ model could be interpreted for the kidney in terms of a half-time of repair of 2.8 h (a negligibly different fit was obtained with the value 1.5 h). The clinical implication could be that multiple-fractions-per-day treatment would benefit from use of the longest feasible interfraction interval when late reactions are dose limiting.

Animals↗
PubMed1988

Accelerated fractionation in the radiation treatment of head and neck cancer. A critical comparison of different strategies.

There is strong clinical and radiobiological evidence that protraction of overall treatment time has an adverse influence on the radiocurability of certain human tumors. Overall treatment time can be reduced without recourse to large dose fractions by the use of accelerated fractionation, but in patients with head and neck cancer acute mucosal reactions limit the extent to which treatment can be accelerated. Three different prototypical schedules for accelerated fractionation have been devised to avoid exceeding acute mucosal tolerance. Type A consists of an intensive short course in which the overall duration of treatment is markedly decreased with a corresponding substantial reduction of total dose; type B achieves a modest decrease in overall time without reduction of total dose by using a split-course technique; type C also achieves a modest decrease in overall time without reduction of total dose by means of the concomitant boost technique. A hybrid schedule combining features of types B and C allows additional shortening of overall treatment time without reduction of total dose. Available radiobiological and clinical data suggest that schedules of types B or C which do not compromise total dose are generally preferable to those of type A in which there is a trade-off between total dose and overall time. For a given total dose and overall time, a continuous treatment of type C is likely to produce more cell kill than a split-course of type B, although the latter will be better tolerated. Because of the increased acute toxicity associated with all schedules of accelerated fractionation, rational selection of patients for such treatment is important. New techniques to measure the potential doubling time of human tumors in vivo offer this prospect.

Clinical Trials as Topic↗
PubMed1988

Tissue repair and repopulation in the tumor bed effect.

These experiments were designed to study the kinetics and magnitude of cell repair and repopulation in tissues whose damage results in the tumor bed effect. The right hind thighs of mice were irradiated with single doses or two equal gamma-ray fractions. Interfraction intervals ranging from 30 min to 24 h (to measure the kinetics of repair from sublethal damage) and 6 and 12 weeks (to determine the extent of repopulation) were used. One day after the second radiation dose 5 X 10(5) FSA tumor cells were inoculated into the center of the irradiated field. Radiation dose-response curves were obtained by calculating the time required for tumors to reach 12 mm diameter. No recovery occurred within 6 h of the radiation delivery as measured by this assay. Some recovery, 3.2-4.6 Gy above a single radiation dose, occurred when the interval between two fractions was 24 h. With increasing interfraction intervals of 6 and 12 weeks further dose sparing occurred in the amount of 5.0-6.9 and 7.5-8.3 Gy, respectively. The data suggest that repopulation is the major contributor to the radiation dose-sparing recovery of stromal tissue and that some proliferative response may occur as early as 1 day after the first irradiation.

Animals↗